Targeting protein folding and post-translational modifications by small molecules: review and prospects

Folding and post-translational modification of proteins are vital for their proper functionality, with various functional regulatory systems playing significant roles, including molecular chaperone systems, ubiquitination systems, phosphorylation systems, acetylation systems, etc. Precise regulations of these systems have emerged as an important trend in drug development. This review systematically summarizes the molecular control strategies related to protein folding and post-translational modification, with a specific focus on the molecular chaperone system and the strategy of heterobifunctional molecules. On one hand, based on the similarities and differences in molecular mechanisms and design strategies, we summarize the drug development process targeting the molecular chaperone system. On the other hand, we discuss the design principles and characteristics of dual-functional molecules, and summarize their applications and developments in the precise control of post-translational modifications, aiming to provide new insights for future design.